| First Author | Cohen I | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 14756 | PubMed ID | 26439902 |
| Mgi Jnum | J:338129 | Mgi Id | MGI:6218494 |
| Doi | 10.1038/srep14756 | Citation | Cohen I, et al. (2015) IL-1alpha is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity. Sci Rep 5:14756 |
| abstractText | Environmental signals can be translated into chromatin changes, which alter gene expression. Here we report a novel concept that cells can signal chromatin damage from the nucleus back to the surrounding tissue through the cytokine interleukin-1alpha (IL-1alpha). Thus, in addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, IL-1alpha could directly sense DNA damage and act as signal for genotoxic stress without loss of cell integrity. Here we demonstrate localization of the cytokine to DNA-damage sites and its subsequent secretion. Interestingly, its nucleo-cytosolic shuttling after DNA damage sensing is regulated by histone deacetylases (HDAC) and IL-1alpha acetylation. To demonstrate the physiological significance of this newly discovered mechanism, we used IL-1alpha knockout mice and show that IL-1alpha signaling after UV skin irradiation and DNA damage is important for triggering a sterile inflammatory cascade in vivo that contributes to efficient tissue repair and wound healing. |
